The basal ganglia are a series of interconnected subcortical nuclei. The function
and dysfunction of these nuclei have been studied intensively in motor control, but
more recently our knowledge of these functions has broadened to include prominent
roles in cognition and affective control. This review summarizes historical models
of basal ganglia function, as well as findings supporting or conflicting with these
models, while emphasizing recent work in animals and humans directly testing the hypotheses
generated by these models.

Anatomically, the perirhinal cortex sits at the boundary between the medial temporal
lobe and the ventral visual pathway. It has prominent interconnections not only with
both these systems, but also with a wide range of unimodal and polymodal association
areas. Consistent with these diverse projections, neurophysiological studies reveal
a multidimensional set of mnemonic signals that include stimulus familiarity, within-
and between-domain associations, associative recall, and delay-based persistence.
This wide range of perirhinal memory signals not only includes signals that are largely
unique to the perirhinal cortex (i.e., object familiarity), consistent with dual-process
theories, but also includes a range of signals (i.e., associative flexibility and
recall) that are strongly associated with the hippocampus, consistent with single-process
theories. These neurophysiological findings have important implications for bridging
the gap between single-process and dual-process models of medial temporal lobe function.

Activity-dependent changes in the strength of synaptic connections are fundamental
to the formation and maintenance of memory. The mechanisms underlying persistent changes
in synaptic strength in the hippocampus, specifically long-term potentiation and depression,
depend on new protein synthesis. Such changes are thought to be orchestrated by engaging
the signaling pathways that regulate mRNA translation in neurons. In this review,
we discuss the key regulatory pathways that govern translational control in response
to synaptic activity and the mRNA populations that are specifically targeted by these
pathways. The critical contribution of regulatory control over new protein synthesis
to proper cognitive function is underscored by human disorders associated with either
silencing or mutation of genes encoding proteins that directly regulate translation.
In light of these clinical implications, we also consider the therapeutic potential
of targeting dysregulated translational control to treat cognitive disorders of synaptic
dysfunction.

According to embodied cognition theories, higher cognitive abilities depend on the
reenactment of sensory and motor representations. In the first part of this review,
we critically analyze the central claims of embodied theories and argue that the existing
behavioral and neuroimaging data do not allow investigators to discriminate between
embodied cognition and classical cognitive accounts, which assume that conceptual
representations are amodal and symbolic. In the second part, we review the main claims
and the core electrophysiological findings typically cited in support of the mirror
neuron theory of action understanding, one of the most influential examples of embodied
cognition theories. In the final part, we analyze the claim that mirror neurons subserve
action understanding by mapping visual representations of observed actions on motor
representations, trying to clarify in what sense the representations carried by these
neurons can be claimed motor.

Elucidating the roles of neuronal cell types for physiology and behavior is essential
for understanding brain functions. Perturbation of neuron electrical activity can
be used to probe the causal relationship between neuronal cell types and behavior.
New genetically encoded neuron perturbation tools have been developed for remotely
controlling neuron function using small molecules that activate engineered receptors
that can be targeted to cell types using genetic methods. Here we describe recent
progress for approaches using genetically engineered receptors that selectively interact
with small molecules. Called "chemogenetics," receptors with diverse cellular functions
have been developed that facilitate the selective pharmacological control over a diverse
range of cell-signaling processes, including electrical activity, for molecularly
defined cell types. These tools have revealed remarkably specific behavioral physiological
influences for molecularly defined cell types that are often intermingled with populations
having different or even opposite functions.

Significant advances have been made in the behavioral assessment and clinical management
of disorders of consciousness (DOC). In addition, functional neuroimaging paradigms
are now available to help assess consciousness levels in this challenging patient
population. The success of these neuroimaging approaches as diagnostic markers is,
however, intrinsically linked to understanding the relationships between consciousness
and the brain. In this context, a combined theoretical approach to neuroimaging studies
is needed. The promise of such theoretically based markers is illustrated by recent
findings that used a perturbational approach to assess the levels of consciousness.
Further research on the contents of consciousness in DOC is also needed.

Recent advances in cell reprogramming enable investigators to generate pluripotent
stem cells from somatic cells. These induced pluripotent cells can subsequently be
differentiated into any cell type, making it possible for the first time to obtain
functional human neurons in the lab from control subjects and patients with psychiatric
disorders. In this review, we survey the progress made in generating various neuronal
subtypes in vitro, with special emphasis on the characterization of these neurons
and the identification of unique features of human brain development in a dish. We
also discuss efforts to uncover neuronal phenotypes from patients with psychiatric
disease and prospects for the use of this platform for drug development.

A major challenge for systems neuroscience is to break the neural code. Computational
algorithms for encoding information into neural activity and extracting information
from measured activity afford understanding of how percepts, memories, thought, and
knowledge are represented in patterns of brain activity. The past decade and a half
has seen significant advances in the development of methods for decoding human neural
activity, such as multivariate pattern classification, representational similarity
analysis, hyperalignment, and stimulus-model-based encoding and decoding. This article
reviews these advances and integrates neural decoding methods into a common framework
organized around the concept of high-dimensional representational spaces.

Although the prevalent view of emotion and decision making is derived from the notion
that there are dual systems of emotion and reason, a modulatory relationship more
accurately reflects the current research in affective neuroscience and neuroeconomics.
Studies show two potential mechanisms for affect's modulation of the computation of
subjective value and decisions. Incidental affective states may carry over to the
assessment of subjective value and the decision, and emotional reactions to the choice
may be incorporated into the value calculation. In addition, this modulatory relationship
is reciprocal: Changing emotion can change choices. This research suggests that the
neural mechanisms mediating the relation between affect and choice vary depending
on which affective component is engaged and which decision variables are assessed.
We suggest that a detailed and nuanced understanding of emotion and decision making
requires characterizing the multiple modulatory neural circuits underlying the different
means by which emotion and affect can influence choices.

Adult neurogenesis, a developmental process of generating functionally integrated
neurons, occurs throughout life in the hippocampus of the mammalian brain and showcases
the highly plastic nature of the mature central nervous system. Significant progress
has been made in recent years to decipher how adult neurogenesis contributes to brain
functions. Here we review recent findings that inform our understanding of adult hippocampal
neurogenesis processes and special properties of adult-born neurons. We further discuss
potential roles of adult-born neurons at the circuitry and behavioral levels in cognitive
and affective functions and how their dysfunction may contribute to various brain
disorders. We end by considering a general model proposing that adult neurogenesis
is not a cell-replacement mechanism, but instead maintains a plastic hippocampal neuronal
circuit via the continuous addition of immature, new neurons with unique properties
and structural plasticity of mature neurons induced by new-neuron integration.